title: PINK1 controls mitochondrial localization of Parkin through direct phosphorylation.
abstract: PTEN-induced putative kinase 1 (PINK1) and Parkin, encoded by their respective genes associated with Parkinson's disease (PD), are linked in a common pathway involved in the protection of mitochondrial integrity and function. However, the mechanism of their interaction at the biochemical level has not been investigated yet. Using both mammalian and Drosophila systems, we here demonstrate that the PINK1 kinase activity is required for its function in mitochondria. PINK1 regulates the localization of Parkin to the mitochondria in its kinase activity-dependent manner. In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this occurrence. These results demonstrate the biochemical relationship between PINK1, Parkin, and the mitochondria and thereby suggest the possible mechanism of PINK-Parkin-associated PD pathogenesis.
authors.affiliation: National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-Dong, Yusong-Gu, Taejon 305-701, Republic of Korea.
authors.forename: Yongsung
authors.initials: Y
authors.lastname: Kim
authors.forename: Jeehye
authors.initials: J
authors.lastname: Park
authors.forename: Sunhong
authors.initials: S
authors.lastname: Kim
authors.forename: Saera
authors.initials: S
authors.lastname: Song
authors.forename: Seok-Kyu
authors.initials: SK
authors.lastname: Kwon
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Tohru
authors.initials: T
authors.lastname: Kitada
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Jongkyeong
authors.initials: J
authors.lastname: Chung
mesh_terms: D000818:Animals; D002460:Cell Line; D004331:Drosophila melanogaster / Q000201:enzymology; D006801:Humans; D008931:Mitochondria, Muscle / Q000201:enzymology*; D010300:Parkinson Disease / Q000201:enzymology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein